Rabies: Jeanne Giese

Rabies: Jeanne Giese Derek Haselman Brown Mackie College

Rabies: Jeanne Giese

Rabies: Jeanne Giese One Sunday morning in mid-September 2004 a bat fluttered into St. Pat's Catholic Church in Fond du Lac, Wisconsin and got knocked to the floor by an usher (Giese, 2010). Fifteen year-old, Jeanna Giese decided it was her duty to get the bat outside to safety. She thought the best way to do so was to grab the bat by the wing tips, and quickly walk outside (Giese, 2010). But, as she walked toward the door the bat began to squeal and jerk to get free. The bat had worked its way to her left hand and buried its fang into her index finger as she stepped outside (Giese, 2010). As she reached a pine tree she had to pry the bat's mouth apart to get it to let go, before she could finally release it onto the tree. As she returned to mass, the threat of rabies did not even cross her mind (Giese, 2010). Giese would later only clean the bite with hydrogen-peroxide (Willoughby et al. 2005). Rabies is a nerve attacking virus that has a short, DNA strand of about 12 nucleic acids (Schnell et al. 2010). Only five proteins are coded for production in this genome strand (Schnell et al. 2010). The rabies virus is most often spread in the saliva of an infected mammal in the form of a bite (How is Rabies Transmitted?, 2011). Another method is getting saliva into a wound is another way transmission is possible (Rabies Fact Sheet, 2002). Contact like petting an animal or with feces, urine, or blood will not pass rabies (Rabies Fact Sheet, 2002). Since the 1960's rabies from dog bites has decreased, and wildlife like raccoons, bats, foxes, and skunks have taken the lead (Jackson, 2001). Wild animals are the most common rabies vector and accounted for 92% of rabies cases in 2010 (Wild Animals, 2011). Raccoons are the major cause of those wildlife rabies cases at 36.5%, followed by skunks at 23.5%. Bats come in third for 23.2% of those wildlife cases (Wild Animals, 2011). In the last twenty years, bat rabies virus has been the major cause of human rabies death in the United states and Canada (Hemachudha et al., 2002). Since 1980 bats have been the cause of 62% of human rabies cases, that has increased in the last twenty years to 75% since 1990 making bats the major cause of human rabies cases (Jackson, 2001). It was not until a month later on Wednesday, October 13th, when Giese took the PSAT that she started feeling tired and sick (Giese, 2010). The long delay between infection and symptoms is called incubation period, and one to three months of incubation is typical (The Path of the Virus, 2011). The length of the period varies between individual cases; the strand of rabies virus, individual immunity, and bite site all affect the time of incubation (The Path of the Virus, 2011). During the incubation time, the virus is carried from the bite site to the brain via the nerves and spinal cord, and the individual is not contagious (The Path of the Virus, 2011). Once in the brain the virus multiplies and inflames the brain, this is the prodromal phase of rabies infection (Hemachudha et al., 2002). This phase can last from two to ten days normally (Jackson, 2001). It then spreads to the salivary glands and saliva, where the individual is now contagious and shows signs of the virus (The Path of the Virus, 2011). This is the point when the host enters the acute neurological phase (Hemachudha et al., 2002).

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The next day was worse for Giese, but she wanted to participate in a volleyball game that night, so she went to school to be eligible to play. By game time she was seeing double and almost fainted multiple times during warm ups (Giese, 2010). She had to sit the bench and kept falling asleep during the game. She was starting to feel the effects of rabies virus: weakness and discomfort (Rabies, 2011). The early symptoms of the virus also include possible fever, headache, sore throat, nausea, vomiting and diarrhea (Jackson, 2001). Giese does not have many memories from the time she got sick until the time she recovered (Giese, 2010). A few scrambled memories is all she can remember; throwing up on a blanket while sitting in a wheelchair, going to the emergency room Saturday night; not being able to balance on one leg; and the doctor looking at and dismissing the healed bat bite as being the cause for her illness (Giese, 2010). That Saturday night she had her first Magnetic Response Imaging, and got lost on the return to the waiting room. Giese was sent home empty handed as to what was wrong (Giese, 2010). Medical providers have trouble diagnosing rabies because many of the symptoms people experience can be nonspecific to rabies and can more easily point to different, more common diseases (Jackson, 2001). The following day, Giese's symptoms had progressed. She was unable to talk or stand, saliva was flooding her mouth, her left arm was twitching and she drifted to and from consciousness (Lite, 2008). She had entered the acute neurological phase, which typically last from two to seventeen days (Jackson, 2001). Two different kinds of rabies, classic and dumb, are possible and evident during the acute neurological phase (Hemachudha et al., 2002). Classic or furious rabies is where signs of rabies are evident and dumb or non-classic rabies is where there are no signs of rabies are evident (Hemachudha et al., 2002). Classic or furious rabies is the rabid rabies type characterized by; host aggravation from noise, thirst or light, breathing irregularity, excess saliva, drifting in and out of consciousness, and changing of phobias i.e. fear of water or flying (Hemachudha et al., 2002). Non-classic or dumb rabies is characterized by; weakness, fear or agitation at night, weakness or partial paralysis, mounding of muscle tissue on chest, deltoid and thigh regions when struck, and a lack of aggression (Hemachudha et al., 2002). Other symptoms like changing phobias and breathing irregularity are less prominent and occur late when they do appear (Hemachudha et al., 2002). Dumb rabies is most likely acquired from a bat and is a bat rabies based strand (Hemachudha et al., 2002). This is the rabies form that Giese most likely had. Another symptom in both kinds of rabies is a tingling feeling at the bite site if rabies was contracted from a bite (What are the Signs and Symptoms of Rabies?, 2011). When Giese returned to the hospital that day she was tested for multiple conditions including meningitis and lime's disease. All the test results returned negative (Giese, 2010). It was then that her mother informed Giese's pediatrician about the bat bite. He took this information along with the symptoms more serious than the first doctor. He took a sample of tissue from her head and body, and then had is sent to the Center for Disease Control (CDC) to test it for rabies (Giese, 2010). In living humans, multiple tests are used to check for rabies. Saliva, spinal fluid, blood plasma, and skin biopsies of hair follicles from the back of the neck are all checked (Diagnosis in Animals & Humans, 2011). The spinal fluid and plasma are checked for the presence of rabies

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antibodies (Diagnosis in Animals & Humans, 2011). Saliva is checked for the presence of the actual rabies virus (Diagnosis in Animals & Humans, 2011). The virus is either found and isolated in the saliva sample or a reverse transcription followed by polymerase chain reaction is used to isolate the presence of the virus (Diagnosis in Animals & Humans, 2011). With the skin biopsy the skin nerves at the base of the hair follicle are examined for rabies virus presence (Diagnosis in Animals & Humans, 2011). These test returned with a rabies positive for Giese. Specifically her spinal fluid and plasma tested positive, while the skin samples and saliva actually showed no signs of the virus yet (Willoughby et al. 2005). With Giese's advanced symptoms, death is typically imminent (Rabies, 2011). Rabies usually too advanced at this stage to cure a patient, survival rate is low by this stage. Dr. Rodney Willoughby from the Children's Hospital of Milwaukee, took on the task to search and develop a new treatment (Lite, 2008). This treatment is now called the Milwaukee Protocol (Lite, 2008). This procedure would require the patient be put into therapeutic coma and administered antiviral drugs while under intensive care (Worcester, 2005). The Milwaukee Protocol's main idea was to stop the brain from becoming injured and using the body's immune system to defeat the virus (Worcester, 2005). He could not promise if Giese would be left braindead or if the treatment would be successful (Giese, 2010). Giese's parents opted for the treatment, over hospice care, to either save their daughters life or allow for the cure for rabies to be furthered (Willoughby et al. 2005). The treatment required Giese's body to destroy the rabies virus, so she was immediately put into a coma (Giese, 2010). She was administered the antivirals ribavarin and amantadine, as well as the anesthetics ketamine and midazolam to help boost her immune system while she was in a coma (Lite, 2008). The drug doses were lowered as the treatment progressed and Giese's immune system kicked into high gear (Worcester, 2005). Dr. Willoughby opted to not give Giese the rabies vaccine or immunoglobulin at this point due to her own natural immune system's response (Worcester, 2005). He was also concerned that it would increase the immune system's response too much and actually harm Giese (Worcester, 2005). Ribavirin was used to protect against rabies inflammation of the brain. This would halt the virus and allow her immune system to clear the virus from her body (Willoughby et al. 2005). Usually with rabies the brain is damaged and then secondary complications result in further injury to the host (Willoughby et al. 2005). This brain damage results in a coma, which is the fourth stage of rabies (Jackson, 2001). The brain succumbs to the virus and starts shutting down, which can lead to cardiac or respiratory arrest or those secondary complications (Jackson, 2001). Secondary complications can be either organ system failures or secondary infections (Jackson, 2001). These complications are the major cause of death, the final stage, with rabies as opposed to the virus actually killing the host (Hemachudha et al., 2002). The therapeutic coma was to prevent the secondary complications from arising while the ribavirin reduced brain damage (Willoughby et al. 2005). It was seven full days before Giese was taken out of the coma state (Giese, 2010). On day eight, a lumbar puncture showed higher amounts of rabies antibody present (Worcester, 2005). This was evidence that the procedure was working as intended (Worcester, 2005). After

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a few days out of the coma state, Dr. Willoughby had to force Giese's eyes open (Giese, 2010). She was too weak to open them herself. After her eyes were open, Giese was able to keep them open, but appeared to be staring into space. Dr. Willoughby then asked Giese to glance at her mom, and she did for a few seconds (Giese, 2010). This was proof she had survived the procedure without brain damage. Giese would spend the next twenty-three days in isolation, until she could be deemed free of contagious rabies (Worcester, 2005). The virus had taken the fundamental functions everyone learns at a young age from her. She had to relearn the basic acts of speaking, walking, drinking and eating (Giese, 2010). She would spend the next eleven weeks in the hospital. Her body and mind would have to remember how to do all these basic acts during this time. One day she would gain the use of her mouth back, the next learn to raise her eyebrows (Willoughby et al. 2005). It was small things like moving toes, holding a head up in bed, or a growing attention span that showed Giese's progression back to normal (Willoughby et al. 2005). To communicate in the early days she had to blink her eyes or squeeze a hand, but she eventually gained some of her voice back in the hospital (Johnson, 2011). While in the hospital Giese was on a pill regiment of seventeen pills a day; two at night and fifteen in the morning (Giese, 2010). Each pill was helping to restore her body's supply of essential nutrients she had lost while in the coma (Giese, 2010). When she finally got to head home on January 1, 2005, Giese's family and her were greeted by a crowd of cameras outside the hospital (Giese, 2010). Jeanne Giese was the first person with rabies to not receive pre/post exposure rabies shots and survive at that time. Dr. Willoughby had later suggested that the treatment's success was possibly due to a weakened virus strand, small bite at a far location from the head and a low dose of the initial virus (Willoughby et al. 2005). The rabies virus has eleven different genetic variations, the first variation is the classic rabies virus (Schnell et al. 2010). This genetic variation is the most common strand found today. Dr. Willoughby also admits that the young age and healthy nature of Giese before being bitten would also help host survival (Willoughby et al. 2005). Giese's rehab did not end at the hospital though. She continued the pill regiment, but at a lesser rate for another four months, the most important being tetrahydrobiopterin (Lite, 2008). Tetrahydrobiopterin is essentially a B-complex vitamin folic acid and is what helped her motor abilities and speech progress faster (Lite, 2008). It was apparent at Giese's first follow-up visit, about three months later, in March, that her rehab was working (Worcester, 2005). She was even able to go back to school part time by then (Worcester, 2005). Giese had spasmodic movements of limbs and muscles that would affect her fine-motor skills and walking (Worcester, 2005). She gave up all three high school sports as she could never run or balance the same as before (Johnson, 2011). She continued to have some speech problems, particularly with tong and cheek articulation (Worcester, 2005). Within a year though, she was just about back up to pre-exposure abilities (Worcester, 2005). Since rabies cases are low in the United States (US) health care professionals are unfamiliar with rabies first hand and rabies is typically not a possible option for diagnosis at first

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(Jackson, 2001). This can lead to the Milwaukee Protocol as the only option, if discovered too late and symptoms progress too far. The Milwaukee Protocol has been marked with low success rates. Out of 35 cases only 4 have survived rehab and made it past the critical point (Willoughby R. E., 2009). This results in only a 11% chance of survival if rabies goes unchecked until too late (Willoughby R. E., 2009). Prevention is the only 100% effective method to deter rabies (Jackson, 2001). Other methods like the post exposure vaccine, given before symptoms occur, have a 100% success rate in the United States (Jackson, 2001). There are two types of vaccines cell culture and non-cell cultured vaccines; the major difference between the two is that cell cultured tend to be purified before use (Jackson, 2001). Modern cell cultured vaccines have the highest safety and efficacy records of both vaccine types. Two major cell culture vaccines are available today in the US, RabAvert (TM) and Imovax(R) Rabies (Jackson, 2001). RabAvert has been around since 1984 and became approved for use in the US in 1997. It is a produced by Chiron Corporation and is a Purified chick embryo cell vaccine (Jackson, 2001). RabAvert is injected into a muscle, i.e. arm, and can be used both as a pre- and post- exposure vaccine. Imovax is made by Avenis Pasteur, Inc. and is a human diploid cell vaccine (Jackson, 2001). It precedes RabAvert's approval in the US by seventeen years. Imovax has the ability to be injected into muscle as well as just under the skin (Jackson, 2001). Both vaccines have shown fast and long-term rabies antibody reaction (Jackson, 2001). For people with repeated exposures or high risk of contraction, booster shots can be administered. These booster vaccinations give similar responses to rabies antibodies (Jackson, 2001). Generally the antibody levels are checked every six months to two years, to notify when boosters are needed. A few side effects of the vaccines include redness of skin, pain, or possible itching at the site of injection (Jackson, 2001). Other more common side effects can be a headache, abdominal pain or nausea, dizziness and muscle aches (Jackson, 2001). Non-cell cultured vaccines are unpurified vaccines made from animal brain tissue (Jackson, 2001). These vaccines are inexpensive and are still widely used around the world. These produce many side effects as well, making these unpopular in developed countries (Jackson, 2001). Non-cell cultured vaccines are the original type of rabies vaccine produced in the 1880's by Louis Pasteur, E. Roux, T. Thuillier, and C. Chamberland (Pearce, 2002). Pasteur, a French chemist, was intrigued with Victor Galtier's immunization of sheep (Pearce, 2002). Using a rabies saliva serum injected into veins, Galtier was able to reduce chances of the sheep catching the rabies. Pasteur started working with rabies in the 1880's and was watching the strength of the rabies strand as it was passed from host to host (Pearce, 2002). He learned how the virus gets weaker as it gets transmitted to different host as well as how it gets stronger. This allowed him to eventually cultivate a vaccine for dogs from rabbit spinal cords. His initial testing worked on fifty dogs (Pearce, 2002). It was shortly after the vaccine discovery that Joseph Meister contracted rabies from a dog bite in 1885, and was taken to see Pasteur (Pearce, 2002). Pasteur was persuaded to give fourteen injections, over an eleven day period, with progressively stronger rabies strands. After three months Meister was given a clean bill of health by Pasteur (Pearce, 2002). Pasteur then

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replicated his work in the fall of the year, and by 1886 he had cured about 350 patients. Pasteur later went on to discovery rabies in the blood stream (Pearce, 2002). Pasteur paved the way for rabies vaccine development. Aldechi Negri developed microscopic diagnosis of rabies, while Fermi developed a Fermi rabies vaccine in 1908 (Pearce, 2002). By 1936 rabies was cultivated in a tissue sample by Webster and Clow (Pearce, 2002). This tissue culture method would eventually allow for human cell culture vaccines and diploid cell vaccines (Pearce, 2002). Over the years due to cost, the vaccination's shorter duration (only 2 years at most) and potential for side effects vaccines have not been recommended for general vaccinations as preventative pre-incident measures (Jackson, 2001). Rabies immunoglobulin was developed to address that issue. Immunoglobulin is essentially rabies antibodies that are injected into the bite area and a distant location from the bite into muscle. It is designed to help your body combat rabies until it is producing antibodies on its own. Rabies immunoglobulin is typically given with a vaccine for rabies post-exposures. Immunoglobulin is only given once, and works before or within seven days of a post-exposure vaccine. The body is assumed to be producing antibodies after the seventh day (Rabies vaccines: WHO position paper/Vaccins antirabiques: note d'information de l'OMS, 2010). Without post-exposure treatments approximately 327,000 people yearly would die from rabies in Asia and Africa (Rabies vaccines: WHO position paper/Vaccins antirabiques: note d'information de l'OMS, 2010). Since preventative measures have been available international rabies only causes 55,000 deaths worldwide each year, most of which still happen in rural areas of Africa and Asia. The top two regions are India accounting for 20,000 deaths and Africa 24,000 deaths. These numbers are lower than the actual number of cases, a number of cases fail to seek medical attention and thus never reported. Over 15 million people get rabies treatment yearly according to rabies vaccine manufacture's data. Data also suggest that children age fifteen and younger, especially males, are more commonly seeking medical attention for rabies (Rabies vaccines: WHO position paper/Vaccins antirabiques: note d'information de l'OMS, 2010). Rabies is a nerve attacking virus that works its way to the brain and eventually causes the demise of the host. Rabies kills an estimated 55,000 people annually worldwide, most cases arise in Asia and Africa (Rabies vaccines: WHO position paper/Vaccins antirabiques: note d'information de l'OMS, 2010). Many of these cases seek medical attention too late or get miss diagnosed (Lite, 2008). In the US, in the last twenty years, over 75% of cases have been caused by bats. It was not until about eight years ago, that if vaccinations were not administered in time victims usually died (Johnson, 2011). Jeanne Giese was the first rabies survivor using the Milwaukee Protocol, and only has minor side effects today. Other modern vaccines exist and still prove to be a more successful method of rabies patient management.

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Works Cited Diagnosis in Animals & Humans. (2011, September 20). Retrieved March 7, 2012, from Center for Disease Control website: http://www.cdc.gov/rabies/diagnosis/animals-humans.html Giese, J. (2010). My Story. Retrieved February 27, 2012, from site.jeannagiese.com: http://site.jeannagiese.com/My_Story.html Hemachudha, T. L. (2002, June). Human Rabies: a Disease of Complex Neuropathogenetic Mechanisms and Diagnostic Challenges. The Lancet Neurology, 1, 101-109. How is Rabies Transmitted? (2011, April 22). Retrieved March 7, 2012, from Center for Disease Control website: http://www.cdc.gov/rabies/transmission/index.html Jackson, A. C. (2001, October). Rabies: Risks, Recognition, and Prophylaxis. Formulary, 36, 314. Retrieved March 7, 2012, from Formulary: http://search.proquest.com.brownmackie.libproxy.edmc.edu/docview/229991927?accoun tid=131689 Johnson, M. (2011, May 8). Rabies survivor Jeanna Giese graduates from college . Retrieved February 27, 2012, from jsonline.com: http://www.jsonline.com/news/wisconsin/121479779.html Lite, J. (2008, October 2008). Medical Mystery: Only One Person Has Survived Rabies without Vaccine--But How? Retrieved February 27, 2012, from scientificamerican.com: http://www.scientificamerican.com/article.cfm?id=jeanna-giese-rabies-survivor Matthias J. Schnell, J. P. (2010, January). The cell biology of rabies virus: using stealth to reach the brain. Nature Review Microbiology, 8, 51-60. doi:10.1038/nrmicro2260 Pearce, J. M. (2002, July). Historical note: Louis Pasteur and rabies: A brief note. Journal of Neurology, Neurosurgery and Psychiatry, 73(1), 82. Retrieved March 13, 2012, from http://search.proquest.com.brownmackie.libproxy.edmc.edu/docview/195728327?accoun tid=131689 Rabies. (2011, December 6). Retrieved March 7, 2012, from Center for Disease Control website: http://www.cdc.gov/rabies/ Rabies Fact Sheet. (2002, May). Retrieved March 14, 2012, from Maryland Department of Health & Mental Hygiene- Epidemiology & Disease Control Program: http://ideha.dhmh.maryland.gov/IDEHASharedDocuments/rabies.pdf Rabies vaccines: WHO position paper/Vaccins antirabiques: note d'information de l'OMS. (2010, August 6). Weekly Epidemiological Record, 85(32), 309-320. Retrieved March 13, 2012, from

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http://search.proquest.com.brownmackie.libproxy.edmc.edu/docview/747686785?accoun tid=131689 The Path of the Virus. (2011, April 22). Retrieved March 7, 2012, from Center for Disease Control website: http://www.cdc.gov/rabies/transmission/body.html What are the Signs and Symptoms of Rabies? (2011, April 22). Retrieved March 7, 2012, from Center for Disease Control website: http://www.cdc.gov/rabies/symptoms/index.html Wild Animals. (2011, November 15). Retrieved March 7, 2012, from Center for Disease Control website: http://www.cdc.gov/rabies/location/usa/surveillance/wild_animals.html Willoughby, R. E. (2009, November). Are We Getting Closer to the Treatment of Rabies? Future Virology, 4(6), 563-570. doi:10.2217/fvl.09.52 Willoughby, R. E., Tieves, K. S., Hoffman, G. M., & Ghanayem, N. S. (2005, June 16). Survival after Treatment of Rabies with Induction of Coma. The New England Journal of Medicine, 352(24). Retrieved March 8, 2012, from http://search.proquest.com.brownmackie.libproxy.edmc.edu/docview/223930708?accoun tid=131689 Worcester, S. (2005, July 15). Protocol That Saved Life of a Rabies Patient Requires Further Study. Retrieved March 6, 2012, from Internal Medicine News: http://www.internalmedicinenews.com/specialty-focus/infectious-diseases/single-articlepage/protocol-that-saved-life-of-a-rabies-patient-requires-further-study.html